1. Field of the Invention
The present invention relates to a novel cyclic peptide and its preparation.
2. Description of Related Art
Peptide 6A is a degradation of fibrinogen β chain analogue which has been known to increase coronary artery and femoral artery blood flow. In 1978(1), peptide 6A was first isolated and purified from the β chain of human fibrinogen by Belew et al.(2). The composition of peptide 6A was confirmed as Ala-Arg-Pro-Ala-Lys (SEQ ID NO: 25). This peptide increases coronary artery and femoral artery blood flow in dogs. In 1997, the inventors prepared peptide 6A and its analogues by solution method and observed that these peptides have good potency for relaxing vascula, lowering blood pressure and anti-thrombosis. The synthetic techniques and functions of these compounds have been described in CN Patent No. 1146458. However, in 1990, the inventors observed that peptide 6A had no additional benefit on the parameters of thrombolysis when injected intravenously (i.v.) together with tissue plasminogene activator in dogs with coronary artery thrombosis. The results indicated that peptide 6A might be degraded rapidly by angiotensin-converting enzyme (ACE) in lung during intravenous administration since peptide 6A is the substrate of this enzyme. In addition, peptide 6A and its analogues, which were synthesized by the inventors in 1997, had excellent anti-thrombosis ability, but their half-life in vivo was quite short, consequently unable to exhibit long-term potency.
In order to solve the problems described above, the inventors considered that a cyclic peptide usually has the characteristic of restricted conformations afford good stability toward peptidase. Therefore, the inventors tried to synthesize peptide 6A and its analogues as cyclic forms to avoid degradation caused by ACE; moreover, so that the cyclic compounds will not lose thrombolytic effects. At this moment, a new cyclic compound and also a new technique to convert linear peptide 6A and its analogues to cyclic forms are needed.